The resistance of the sinus node automaticity to high potassium levels have been studied in anesthetized dogs in which perfusion of the sinus node artery was carried out with oxygenated Tyrode solution containing different potassium concentrations. The following results were obtained: (1) sinus node automaticity persists at a concentration of 21.6 mM K, although the pacemaker site may shift in and out of the node at that concentration; (2) sinus node dominance in high potassium is progressively lost as sympathetic influences are progressively eliminated; (3) sinus node pacemaker activity is suppressed at K concentration lower than 21.6 mM K when calcium is omitted from the perfusion fluid; (4) the pacemaker site shifts consistently from the sinus node towards the AV node at high potassium after the elimination of sympathetic activity; and (5) the transient sinus tachycardia caused by high potassium persisted after bilateral vagotomy. It is concluded that the sinus node is more resistant than Purkinje fibers to high potassium because of the abundant sympathetic innervation. The catecholamines released by high potassium perfusion counteract the negative chronotropic effect of potassium, probably by increasing the slow inward currents responsible for excitation.